Despite current and ongoing prevention efforts, domestic HIV infection rates remain high. Behavioral interventions have had important but limited successes in reducing rates of high risk sexual behavior. Methamphetamine use is an expanding epidemic which has been demonstrated to increase rates high-risk sexual behavior and rates of HIV seroconversion in men who have sex with men (MSM). Biomedical HIV-1 prevention strategies are promising multi-disciplinary interventions which have the potential to dramatically impact rates of incident HIV infections with widespread and appropriate uptake. Post-exposure prophylaxis (PEP) is the format of biomedical prevention which is the most advanced, with extensive experience in the occupational arena where PEP efficacy has been estimated to confer 81% reduction in risk of HIV acquisition. There has been little information in the literature on the acceptability, feasibility, or safety of PEP use in methamphetamine-using MSM. This award application is intended to support the applicant's patient oriented career development through mentoring, formal training in biostatistics, qualitative research methods, behavioral prevention methods, and substance abuse prevention and treatment, and informal colloquia and mentored reading. The research aims of this award application are to establish the extent and predictors of PEP knowledge in the methamphetamine-using community and to demonstrate the feasibility, safety, and acceptability of PEP service delivery in methamphetamine-using MSM. These aims will be accomplished via studies nested within 2 currently enrolling cohorts in Los Angeles, California. The data to be generated in the proposed study will allow the design of targeted interventions for investigation via randomized, controlled trials. The studies described in this award application are the first examples of the use of a biomedical HIV-1 prevention strategy specifically designed for substance users. The long-term goals of this research are to provide the foundation for the implementation of biomedical HIV-1 prevention strategies in stimulant-using populations. PUBLIC HEALTH RELEVANCE: Rates of new HIV-1 infections remain high, especially in methamphetamine-using men who have sex with men. Biomedical prevention strategies such as post-exposure prophylaxis (PEP) are promising in their ability to abort HIV-1 infection after sexual exposure to an infected individual. Such strategies, when optimized for substance-using populations, could have a large impact on rates of newly acquired infections.